Epidemiological evidence indicates that environmental factors, in addition to genetic and immunological influences, play a critical pathogenetic role in insulindependent diabetes mellitus (IDDM). N-nitroso compounds and their precursors are ubiquitous environmental pollutants and commonly are present in human food. A number of these compounds exhibit a specificity for pancreatic beta cells and their precursor ductal cells. An understanding of the relative tropism of N-nitroso compounds for pancreatic beta cells is needed to fully elucidate the possible role of theses compounds in the pathogenesis of IDDM. Because of the complexities of N-nitroso metabolism and the difficulties of assaying cytotoxicity in intact animals, studies for this purpose are uniquely suited for tissue culture systems. In this investigation, cultured pancreatic islet and fibroblastiod cells from rats and mice will be used to (1) determine whether beta cells are more sensitive to the toxic effects of specific N-nitroso compounds; (2) ascertain whether beta cells from different species of rodents differ in their sensitivity to N-nitroso compounds and (3) compare the tropism for beta cells of these agents with other islet cells and fibroblastiod cells. The assessment of tropism will be based on changes observed in the morphology, biochemistry and replication of cells exposed to the N-nitroso agents.